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Visible-light-mediated chemical reactions have become very popular within the last 15 years. Many excellent reviews have summarized reaction principles and recent results in photochemistry and photocatalysis. However, despite their popularity photochemistry and photoredox catalysis are not regular parts of the bachelor and master curriculum of chemistry education. As a consequence, most chemists will use in synthesis planning classic retrosynthetic disconnections and only rarely consider photocatalytic steps. The aim of this article is to be a useful tool for synthetic chemists, that are interested in the synthetic aspects of photocatalysis and looking for a specific retrosynthetic disconnection. Not only are informative schemes provided but also are the availability of the catalysts and reagents as well as the functional group tolerance of the respective method briefly discussed.

In the last decade, visible‐light photoredox catalysis has evolved into a versatile tool in organic synthesis. However, most reports have used homemade photoreactors in their design and optimisation of new methods, complicating the reproducibility of some transformations. To improve reproducibility as well as efficiency, laboratory photoreactors have been developed and commercialized. Herein we report a comparison of four commercially available photoreactors in six mechanistically distinct photoredox reactions focusing on the difference in product yields and kinetics as well as the factors, which lead to these differences including reaction temperature and light intensity.

Whereas transition-metal-catalyzed decarbonylative dehydration of fatty acids shows promise as a more sustainable route to α-olefins, the solvents used for this process have so far been toxic compo...

Scientists are exploring renewables as sources for a more sustainable production of chemicals. Linear α-olefins (LAOs) are key commodity chemicals and petrochemical intermediates, which are currently almost exclusively obtained from fossil resources. The most important renewable alternative is plant oil, from which fatty acids and their derivatives can be converted into LAOs by ethenolysis of monounsaturated fatty acids or deoxygenation of saturated ones. The variety, in terms of length, is greater for the saturated fatty acids found in plant oils, and this review covers deoxygenation processes mediated by homogeneous, heterogeneous and enzymatic catalysts and discusses the strengths and weaknesses of different approaches for the selective production of LAOs. Although progress has been made in recent years, the best catalysts in each category are still far from fulfilling the industrial requirements for efficiency, atom economy, and turnover numbers. We hope that our focus on the main remaining challenges will stimulate future research to develop catalysed deoxygenation of fatty acid derivatives as a sustainable and industrially viable route to a range of α-olefins.

A mild, efficient and straightforward visible-light-driven method has been developed to construct 1,2-diarylvinyl sulfides under catalyst- and additive-free conditions. The formation of small amounts of thiyl radicals under visible light irradiation allows the synthesis of 1,2-diarylvinyl sulfides in good yield with an excellent functional group tolerance.

A homogeneous, redox-neutral photo fragmentation of diol derivatives was developed. Under photo/hydrogen atom transfer (HAT) dual catalysis, diol derivatives such as lignin model compounds and diol monoesters undergo selective β C(sp3)–O bond cleavage to afford ketones, phenols and acids effectively.

Nine biotinylated Grubbs-Hoveyda and Grubbs-type metathesis catalysts were synthesized and evaluated in ring closing metathesis reactions of N-tosyl diallylamine and 5-hydroxy-2-vinylphenyl acrylate. Their catalytic activity in organic- and aqueous solvents was compared with the second generation Grubbs-Hoveyda catalyst. The position of the biotin-moiety on the N-heterocyclic carbene was found to critically influence the catalytic activity of the corresponding ruthenium-based catalysts. Graphical Abstract

Heterogeneous catalysts have so far not been very efficient [turnover frequency (TOF) 95%) for one such deoxygenation, decarbonylative dehydration, by using a heterogeneous Pd/C catalyst in the presence of phosphine ligands. The process is solvent free, allows for catalyst recycling, and does not require in situ distillation of the product to maintain high selectivity.

Transition-metal-catalyzed decarbonylative dehydration of even-numbered fatty acids to give valuable odd-numbered alpha olefins has so far been performed using approaches in which the catalyst is formed in situ. We show that well-defined Pd(bis-phosphine) precatalysts eliminate the need for excess phosphine and selectively produce linear alpha olefins under mild conditions and with substantially increased turnover frequency (TOF) and substrate scope. In particular, the new precatalyst Pd(cinnamyl)Cl(DPEPhos) (5) selectively converts substrates containing unprotected aliphatic-alcohol and amine functional groups to their corresponding linear alpha olefins.

The direct reduction of arenes and heteroarenes by visible‐light irradiation remains challenging, as the energy of a single photon is not sufficient for breaking aromatic stabilization. Shown herein is that the energy accumulation of two visible‐light photons allows the dearomatization of arenes and heteroarenes. Mechanistic investigations confirm that the combination of energy‐transfer and electron‐transfer processes generates an arene radical anion, which is subsequently trapped by hydrogen‐atom transfer and finally protonated to form the dearomatized product. The photoreduction converts planar aromatic feedstock compounds into molecular skeletons that are of use in organic synthesis., Splitting the work: Energy transfer (EnT) and photoinduced single‐electron transfer (SET) allow the reduction of arenes. Subsequent hydrogen‐atom transfer (HAT) yields the reduced dearomatized products.

This chapter is a tribute to the leadership and teaching abilities of Anup K Sinha. As an executive coach who comes across people across different walks of life, each and every interaction with Anup K Sinha has been a learning experience for me. The chapter elaborates on the qualities of leadership and how they can be illustrated through the life of Professor Anup K Sinha.

Linear alpha olefins (LAOs) are key commodity chemicals and petrochemical intermediates that are currently produced from fossil resources. Fatty acids are the obvious renewable starting material for LAOs, which can be obtained via transition-metal-catalyzed decarbonylative dehydration. However, even the best catalysts that have been obtained to date, which are based on palladium, are not active and stable enough for industrial use. To provide insight for design of better catalysts, we here present the first computationally derived mechanism for another attractive transition-metal for this reaction, rhodium. By comparing the calculated mechanisms and free energy profiles for the two metals, Pd and Rh, we single out important factors for a facile, low-barrier reaction and for a stable catalyst. While the olefin formation is rate limiting for both of the metals, the rate-determining intermediate for Rh is, in contrast to Pd, the starting complex, (PPh3)2Rh(CO)Cl. This complex largely draws its stability from the strength of the Rh(I)–CO bond. CO is a much less suitable ligand for the high-oxidation state Rh(III). However, for steric reasons, rhodium dissociates a bulkier triphenylphosphine and keeps the carbonyl during the oxidative addition, which is less favorable than for Pd. When compared to Pd, which dissociates two phosphine ligands at the start of the reaction, the catalytic activity of Rh also appears to be hampered by its preference for high coordination numbers. The remaining ancillary ligands leave less space for the metal to mediate the reaction.

The palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of organic halides with boronic acids is one of the most versatile methods for the synthesis of biaryls. Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. When designed properly, clean chemical technology can be developed in water as a reaction medium. The technologies generated from such green chemistry endeavours may often be cheaper and more profitable. This review covers the literature on palladium-catalysed the Suzuki–Miyaura cross-coupling reaction in water.

(R)-(+)-Trichostatic acid and (R)-(+)-trichostatin A (TSA) are natural products that have attracted considerable attention in the field of epigenetic therapies. TSA in particular is a naturally occurring hydroxamic acid having potent activity as a histone deacetylase inhibitor (HDACi) and having significant potential for treatment of a myriad of genetically based diseases. Development of TSA and other trichostatic acid derivatives into useful small-molecule therapies has been hindered by the low natural abundance and high cost associated with these compounds. We report herein our collective efforts towards the development of concise and scalable routes for the synthesis of trichostatic acid and TSA in both racemic and enantioenriched forms. Three independent synthetic pathways were developed with varying degrees of efficiency and convergency. In the first synthesis, the key step was a vinylogous Horner-Wadsworth-Emmons condensation. A Marshall propargylation reaction was used as the key step in the second synthesis, and Pd-catalyzed a-alkenylation of a ketone zinc enolate by using various functionalized alkenyl or dienyl halides was developed for the third synthesis. The second pathway proved to be readily amenable to an enantioselective modification, and both the second and third pathways were straightforwardly adapted for the facile preparation of new analogues of trichostatic acid and TSA.

The fluoroallylboration of aldehydes with B-(3,3-difluoroallyl)diisopinocampheylborane, which was prepared via the hydroboration of 1,1-difluoroallene, provides chiral 2,2-gem-difluorinated homoallylic alcohols in good yields and 91-97% ee.

Niemann-Pick type C (NPC) disease is predominantly caused by mutations in the NPC1 protein that affect intracellular cholesterol trafficking and cause accumulation of unesterified cholesterol and other lipids in lysosomal storage organelles. We report the use of a series of small molecule histone deacetylase (HDAC) inhibitors in tissue culture models of NPC human fibroblasts. Some HDAC inhibitors lead to a dramatic correction in the NPC phenotype in cells with either one or two copies of the NPC1 I1061T mutation, and for several of the inhibitors, correction is associated with increased expression of NPC1 protein. Increased NPC1 I1061T protein levels may partially account for the correction of the phenotype, because this mutant can promote cholesterol efflux if it is delivered to late endosomes and lysosomes. The HDAC inhibitor treatment is ineffective in an NPC2 mutant human fibroblast line. Analysis of the isoform selectivity of the compounds used implicates HDAC1 and/or HDAC2 as likely targets for the observed correction, although other HDACs may also play a role. LBH589 (panobinostat) is an orally available HDAC inhibitor that crosses the blood–brain barrier and is currently in phase III clinical trials for several types of cancer. It restores cholesterol homeostasis in cultured NPC1 mutant fibroblasts to almost normal levels within 72 h when used at 40 nM. The findings that HDAC inhibitors can correct cholesterol storage defects in human NPC1 mutant cells provide the potential basis for treatment options for NPC disease.

The reaction of β-benzyloxy-γ,γ-difluoroallylboronate, at room temperature and in the absence of catalysts, with a variety of aromatic and aliphatic ketones of varying sterics and electronic requirements furnishes fluorinated homoallylic tert-alcohols in 62–82% yields. Representatives of these alcohols were converted to their corresponding α,α-difluoro-β-hydroxy ketones in 73–85% yields.

The palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of organic halides with boronic acids is one of the most versatile methods for the synthesis of biaryls. Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. When designed properly, clean chemical technology can be developed in water as a reaction medium. The technologies generated from such green chemistry endeavours may often be cheaper and more profitable. This review covers the literature on palladium-catalysed the Suzuki–Miyaura cross-coupling reaction in water.

Introduction of a biotinylated monophosphine palladium complex within streptavidin affords an enantioselective artificial Suzukiase. Site-directed mutagenesis allowed the optimization of the activity and the enantioselectivity of this artificial metalloenzyme. A variety of atropisomeric biaryls were produced in good yields and up to 90% ee., Introduction of a biotinylated monophosphine palladium complex within streptavidin affords an enantioselective artificial Suzukiase. Site-directed mutagenesis allowed the optimization of the activity and the enantioselectivity of this artificial metalloenzyme. A variety of atropisomeric biaryls were produced in good yields and up to 90% ee. The hybrid catalyst described herein shows comparable TOF to the previous aqueous-asymmetric Suzuki catalysts, and excellent stability under the reaction conditions to realize higher TON through longer reaction time.

An efficient synthesis of rac-trichostatic acid (1) and its analogues is reported starting from a commercially available aldehyde. Further manipulations of rac-1 led to rac-trichostatin A (TSA). Construction of the desired molecular architecture entails a two-component union, achieved through an in situ hydroboration followed by a Suzuki-Miyaura coupling with 2. The requisite homopropargyl alcohol was synthesized by exploiting allenylindium chemistry. This new protocol paved the way for the synthesis of analogues of trichostatic acid and hence TSA.

Treatment of difluoroallene (I) with HB(Ipc)2 provides the allylborane (II) whose reaction with various aldehydes allows highly enantioselective access to 2,2-difluorinated homoallylic alcohols.

A novel cage-annulated (bis-homocubyl) vinylidenecarbene has been generated and successfully trapped without any intermediacy of its cycloalkyne isomer. The greater kinetic and thermodynamic stability of the vinylidenecarbene vis-a-vis its cycloalkyne isomer has been predicted by DFT B3LYP/6-31G* calculations. The calculated results suggest the prospects of the cycloalkyne becoming amenable for trapping, if generated under suitable experimental conditions, owing to the substantial kinetic energy barrier associated with its possible ring contraction via 1,2-shift to the vinylidenecarbene isomer and marginal ground state energy difference. However, all of our attempts to directly generate and trap the cycloalkyne yielded unsatisfactory results. Attempted generation and trapping of a C2-symmetric bis-vinylidenecarbene from a bis-vinylidenedibromide met with unexpected failure.

Still—Gennari olefination of substrates (II) affords exclusively the (Z)-isomers (IV) which are transformed to the required pyrones (VI) (important building blocks of natural products) via (Z)-alcohols (V).

Horner-Wadsworth-Emmons (HWE) or Still-Gennari olefination of TBS-protected 3,3-difluoro-4-hydroxy-2-ones, derived from the difluoroallylboration of aldehydes, provides the Z-isomer of 4,4,-difluoropent-2-enoates. These, upon hydrolysis, followed by Yamaguchi cyclization, afford 5,5-difluoro-4-methyl-5,6-dihydro-α-pyrones in high yields.

The reaction of β-benzyloxy-γ,γ-difluoroallylboronate, at room temperature and in the absence of catalysts, with a variety of aromatic and aliphatic ketones of varying sterics and electronic requirements furnishes fluorinated homoallylic tert-alcohols in 62–82% yields. Representatives of these alcohols were converted to their corresponding α,α-difluoro-β-hydroxy ketones in 73–85% yields.

Gamma,gamma-difluoroallylboronates have been prepared from trifluoroethanol and utilized for the allylboration of a variety of aldehydes to provide gem-difluorinated homoallylic alcohols. Alpha-chiral aldehydes were allylborated in 4:1-13:1 diastereoselectivity favoring the anti-isomer. A representative series of difluorinated hydroxyl enol ethers were converted to the corresponding alpha,alpha-difluoro-beta-hydroxy ketones. Diastereoselective reduction of one of these to either syn- and anti-1,3-diol was also studied.